This is an open-label, repeat-dose, intra-subject dose escalation study of SBC-102 (USAN: sebelipase alfa) in children with growth failure due to LAL Deficiency. Eligible subjects will receive once-weekly (qw) infusions of sebelipase alfa for up to 5 years

An Open Label, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SBC-102 (Sebelipase Alfa) in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency

The percentage of subjects achieving transfusion-free hemoglobin normalization (TFHN) of ≥ 4 weeks at any time during the study (also referred to as short-term TFHN), and the percentage of subjects who maintained TFHN for ≥ 13 weeks beginning at Week 6 (also referred to as sustained early TFHN). A subject was considered to have achieved short-term TFHN if the/she had two post-baseline measurements of hemoglobin, obtained at least 4 weeks apart, that were above the age-adjusted lower limit of normal (LLN), and had no additional hemoglobin measurements below LLN during this minimum 4-week period and no transfusions administered during the minimum 4-week period or for 2 weeks prior to the start of this period.

All subjects received IV infusions of sebelipase alfa during the open-label treatment period. Subjects received a starting dose of 0.35 mg/kg once weekly (qw) and, after demonstrating acceptable safety and tolerability after at least 2 infusions at this dose, began receiving the per-protocol dose of 1 mg/kg qw. Thereafter, subjects were to continue receiving a dose of 1 mg/kg qw for the duration of the treatment period. However, in the event of disease progression (based on protocol-defined criteria) at any time during treatment with 1 mg/kg qw, an individual subject could receive a dose increase to 3 mg/kg qw and; if necessary, a subsequent dose increase to 5 mg/kg qw (after review and approval by a Safety Committee). Subjects receiving long-term treatment on a stable qw dose could be switched to an every other week (qow) dosing schedule at the same total dose (mg/kg) per infusion.

Drug: Sebelipase alfa (SBC-102)

Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). The investigational medicinal product is an enzyme replacement therapy intended for treatment of patients with LAL Deficiency. Dosing will occur once weekly for up to three years.

Detailed Description:

Lysosomal Acid Lipase (LAL) Deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of LAL, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. Although a single disease, LAL Deficiency presents as a clinical continuum with two major phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease.

Early Onset LAL Deficiency (Wolman Disease) is extremely rare, with an estimated incidence of less than 2 lives per million. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first year of life. There is currently no approved therapy for the treatment of LAL Deficiency.

Male or female child with documented decreased LAL activity relative to the normal range of the lab performing the assay or documented result of molecular genetic testing (2 mutations) confirming a diagnosis.

Growth failure with onset before 6 months of age.

Exclusion Criteria:

Clinically important concurrent disease.

Has received an investigational product other than sebelipase alfa within 14 days prior to the first dose.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01371825